Exploring the utility of 3D-skin models to evaluate trans-dermal uptake of flame retardants from indoor dust and consumer products

The aim of this research was to evaluate the utility of innovative $in$ $vitro$ techniques as an alternatives for human/animal tissues to study the transdermal uptake of organic flame retardants from indoor dust and consumer products. Firstly, we successfully designed and applied an $in$ $vitro$ physiologically based extraction test to provide new insights into the dermal bioaccessibility of various FRs from indoor dust. These investigations revealed the bioaccessible fraction for the brominated flame retardants (BFRs) α-, β-and γ- HBCD and TBBPA to 1:1 (sweat/sebum) mixture to be 41%, 47%, 50% and 40%, respectively, while for the phosphate flame retardants (PFRs) TCEP, TCIPP and TDCIPP, the values were 10%, 17% and 19%. With the exception of TBBP A, the presence of cosmetics had a significant effect (p <0.05) on the bioaccessibility of our target FRs from indoor dust. The presence of cosmetics decreased the bioaccessibility of HBCDs from indoor dust, whereas shower gel and sunscreen lotion enhanced the bioaccessibility of target PFRs. Secondly, we developed a protocol for studying dennal uptake of legacy and novel brominated flame retardants using two 3D-HSE (three dimensional human skin equivalent tissue) models, EpiDerm™ and EPISKIN™ in compliance with the OECD guidelines 428. Overall, results showed a significant negative correlation between the permeability constant of FRs and their Log K$_o$$_w$ values. We also mimicked real life exposure scenarios by exposing the skin surface in turn to FR-containing dust, reference material plastics and upholstered fabrics. Our findings showed that under such scenarios dermal exposure to FRs was appreciable for UK adults and toddlers. For example, for dust exposure, our estimates of daily intake indicated toddlers to be 10 times more highly exposed than adults in the presence of sweat and sebum. This differential exposure is likely attributable to more dust adhering to toddler's skin and their higher exposed skin surface area to body weight ratio compared to adults

MICRONEEDLES: NOVEL APPROACH TO TRANDERMAL DRUG DELIVERY SYSTEM

Excellent impervious nature of skin is the greatest challenge that has to be overcome for successfully delivering drug molecules to the systemic circulation by this route. Various formulation approaches used to systemically deliver drug molecules include use of prodrugs/lipophilic analogs, permeation enhancers, sub saturated systems and entrapment into vesicular systems. Further, the adhesive mixture, physical system of the delivery system and release liner influence drug release and its permeation across the skin. The novel microneedle dual-delivery method combines the advantages of hypodermic syringes and transdermal patches. Composed of dozens to hundreds of hollow microneedles, a (1–2)cm2 transdermal patch is applied to the skin to increase its permeability. An array of microneedles that are 100–1000 μm in length poke through the top layers of skin and allow micron-scale drugs to pass into the body. The needles are too small to stimulate nerve endings; patients wouldn’t feel any pain when a microneedle injection is performed. This review gives an overview of microneedles for drug delivery applications. The concept of miniaturized needles is presented and defined. Specific requirements for microneedles aimed for transdermal drug delivery are discussed and the scope is delimited. Some of the basic microfabrication methods used to fabricate microneedles is introduced and microneedles for drug delivery presented so far are reviewed and commented.Keywords: Transdermal drug delivery, microneedles, transcutaneous permeation, percutaneous permeation, Microelectromechanical Systems. Â

Lipid-dependent conformational landscape of the ErbB2 growth factor receptor dimers

Altered lipid metabolism has been linked to cancer development and progression. Several roles have been attributed to the increased saturation and length of lipid acyl tails observed in tumors, but its effect on signaling receptors is still emerging. In this work, we have analyzed the lipid dependence of the ErbB2 growth factor receptor dimerization that plays an important role in the pathogenesis of breast cancer. We have performed coarse-grain ensemble molecular dynamics simulations to comprehensively sample the ErbB2 monomer-dimer association. Our results indicate a dynamic dimer state with a complex conformational landscape that is modulated with increasing lipid tail length. We resolve the native N-terminal "active" and C-terminal "inactive" conformations in all membrane compositions. However, the relative population of the N-terminal and C-terminal conformers is dependent on length of the saturated lipid tails. In short-tail membranes, additional non-specific dimers are observed which are reduced or absent in long-tailed bilayers. Our results indicate that the relative population as well as the structure of the dimer state is modulated by membrane composition. We have correlated these differences to local perturbations of the membrane around the receptor. Our work is an important step in characterizing ErbB dimers in healthy and diseased states and emphasize the importance of sampling lipid dynamics in understanding receptor association

Smart Yoga Assistant: SVM-based Real-time Pose Detection and Correction System

SVM-based Real-time Pose Detection and Correction System refer to a computer system that uses machine learning techniques to detect and correct a person's yoga pose in real-time. This system can act as a virtual yoga assistant, helping people improve their yoga practice by providing immediate feedback on their form and helping to prevent injury. This paper presents a yoga tracker and correction system that uses computer vision and machine learning algorithms to track and correct yoga poses. The system comprises a camera and a computer vision module that captures images of the yoga practitioner and identifies the poses being performed. The machine learning module analyzes the images to provide feedback on the quality of the poses and recommends corrections to improve form and prevent injuries. This paper proposed a customized support vector machine (SVM) based real-time pose detection and correction system that suggests yoga practices based on specific health conditions or diseases. Paper aims to provide a reliable and accessible resource for individuals seeking to use yoga as a complementary approach to managing their health conditions. The system also includes a practitioner’s interface that enables practitioners to receive personalized recommendations for their yoga practice. The system is developed using Python and several open-source libraries, and was tested on a dataset of yoga poses. The hyper parameter gamma tuned to optimize the classification accuracy on our dataset produced 87% which is better than other approaches. The experiment results demonstrate the effectiveness of the system in tracking and correcting yoga poses, and its potential to enhance the quality of yoga practice

Dip coating of forsterite-hydroxyapatitie-poly (ɛ-caprolactone) nanocomposites on Ti6Al4Vsubstrates for its corrosion prevention

522-528Titanium and titanium alloys are extensively used in biomedical, cardiac and cardiovascular applications for their superb properties, such as good fatigue strength, low modulus, machinability, formability, corrosion resistance and biocompatibility. However, titanium and its alloys do not meet the majority of all clinical necessities. Due to these reasons, surface modification is frequently performed to enhance the mechanical, biological and chemical properties of titanium and alloys. In this work, nanocomposites coating of poly(ɛ-caprolactone)/hydroxyapatite/forsterite (PCL/HA/F) have been successfully deposited on the Ti6Al4V substratesby dip coating at room temperature. The coatings are prepared with various concentrations of forsterite/hydroxyapatite nanopowder (2, 4, 6 and 8 wt.%) with a fixed concentration of PCL (4 wt.%) and thus coated Ti6Al4V substrates are examined for corrosion resistance. PCL/Hydroxyapatite/Forsterite coatings are characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM), which clearly showed the formation of nanocomposites. Potentiodynamic polarization curves and electrochemical impedance spectroscopy (EIS) are used to investigate corrosion behavior of the coated substrates, which portrayed that the composite coating of PCL/HA/F substantially enhanced the corrosion resistance of Ti6Al4V alloy

Dip coating of forsterite-hydroxyapatitie-poly (ɛ-caprolactone) nanocomposites on Ti6Al4Vsubstrates for its corrosion prevention

Titanium and titanium alloys are extensively used in biomedical, cardiac and cardiovascular applications for their superb properties, such as good fatigue strength, low modulus, machinability, formability, corrosion resistance and biocompatibility. However, titanium and its alloys do not meet the majority of all clinical necessities. Due to these reasons, surface modification is frequently performed to enhance the mechanical, biological and chemical properties of titanium and alloys. In this work, nanocomposites coating of poly(ɛ-caprolactone)/hydroxyapatite/forsterite (PCL/HA/F) have been successfully deposited on the Ti6Al4V substratesby dip coating at room temperature. The coatings are prepared with various concentrations of forsterite/hydroxyapatite nanopowder (2, 4, 6 and 8 wt.%) with a fixed concentration of PCL (4 wt.%) and thus coated Ti6Al4V substrates are examined for corrosion resistance. PCL/Hydroxyapatite/Forsterite coatings are characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM), which clearly showed the formation of nanocomposites. Potentiodynamic polarization curves and electrochemical impedance spectroscopy (EIS) are used to investigate corrosion behavior of the coated substrates, which portrayed that the composite coating of PCL/HA/F substantially enhanced the corrosion resistance of Ti6Al4V alloy